A convenient and efficient one-pot synthesis of arylacetones from (E)-3-aryl-2-methylacrylic acids by curtius rearrangement

Article abstract of DOI:10.1055/s-0036-1588905

A convenient and efficient method was developed for the synthesis of arylacetones from (E)-3-aryl-2-methylacrylic acids through a Curtius rearrangement. The Curtius rearrangement of (E)-3-aryl-2-methylacryloyl azides and subsequent hydrolysis proceeded at mild temperatures in a two-phase medium of carbon tetrachloride and water containing a catalytic amount of tetrabutylammonium bromide to give the corresponding derivatives in 82-93% yield.

Full text of DOI:10.1055/s-0036-1588905

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
letter
A
X. He et al.
Letter
Synlett
A Convenient and Efficient One-Pot Synthesis of Arylacetones
from (E)-3-Aryl-2-methylacrylic Acids by Curtius Rearrangement
Xin He
1. SOCl2, CCl4
COOH
Chong Cao
Jingwei Liang
Xinyang Li
R
R
O
2. 20 mol% NaN3, 10 mol% TBAB, reflux
9 examples
82–93% yield
R = H, OMe, NO2, Cl
Tingjian Zhang
Fanhao Meng*
Department of Medicinal Chemistry, School of Pharmacy,
China Medical University, No. 77 Puhe Road, Shenyang,
Liaoning, 110122, P. R. of China
fhmeng@cmu.edu.cn
Received: 15.08.2016
Accepted after revision: 05.10.2016
Published online: 26.10.2016
route need to be improved. First, obtaining the benzyl-
zinc(II) chloride derivatives is difficult because of the low
reactivity of zinc under the experimental conditions, and
the consequent need for anhydrous conditions. Secondly,
the precise reaction temperature is difficult to control. On
increasing the reaction temperature, an alcoholic byprod-
uct can be formed in the reaction system. A similar synthet-
ic strategy involving the nucleophilic addition of a benzyl-
magnesium chloride with acetonitrile, followed by hydroly-
sis, gives the corresponding phenylacetone in a good yield
(Scheme 2). Unlike benzylzinc(II) chlorides, which are diffi-
cult to obtain because of the relative chemical inactivity of
zinc, nucleophilic benzylmagnesium chlorides can be easily
prepared and show a high reaction potential. Moreover, af-
ter nucleophilic addition of the benzylmagnesium chloride
to acetonitrile, the intermediate imine is relatively stable
and does not react with the benzylmagnesium chloride to
form byproducts. However, it was found to be difficult to
avoid the formation of a dimer through the alkylation of the
benzylmagnesium chloride with the benzyl chloride during
the preparation of the benzylmagnesium chloride (Scheme 2).
Inspired by the reaction mechanism of this method, we
designed and developed a novel method for the preparation
of arylacetones by using inexpensive commercially avail-
able compounds to form imines, instead of using Grignard
reagents, eventually giving the target compounds through
hydrolysis. We hypothesized that the carboxylic acid group
directly connected to the unsaturated double bond in the
aliphatic hydrocarbon moiety of (E)-3-aryl-2-methylacrylic
acids might be used to introduce the skeleton of an imide. If
the carboxylic acid group was replaced by an amine group,
3-aryl-2-methylacrylic acids might be converted into the
corresponding 1-arylprop-1-en-2-amines. These could then
be converted into 1-arylpropan-2-imines by tautomeriza-
tion. On this basis of this hypothesis, we developed a novel
synthetic route for the synthesis of arylacetones by convert-
DOI: 10.1055/s-0036-1588905; Art ID: st-2016-w0529-l
Abstract A convenient and efficient method was developed for the
synthesis of arylacetones from (E)-3-aryl-2-methylacrylic acids through
a Curtius rearrangement. The Curtius rearrangement of (E)-3-aryl-2-
methylacryloyl azides and subsequent hydrolysis proceeded at mild
temperatures in a two-phase medium of carbon tetrachloride and wa-
ter containing a catalytic amount of tetrabutylammonium bromide to
give the corresponding derivatives in 82–93% yield.
Key words arylacetones, Curtius rearrangement, methylarylacrylic ac-
ids, phase-transfer catalysis, acryloyl azides
Arylacetones are important synthetic building blocks
with a wide range of applications in the fine chemical, ag-
rochemical, and pharmaceutical industries.1–3 For instance,
1-(4-methoxyphenyl)acetone is an important intermediate
for the synthesis of tamsulosin hydrochloride, a drug for the
treatment of benign prostatic hyperplasia; 1-(3,4-dime-
thoxyphenyl)acetone
and
1-(3,4-methylenedioxyphe-
nyl)acetone are used as raw materials, critical for the prepa-
ration of methyldopa; and 1-(2-methoxyphenyl)acetone is
a key intermediate for the preparation of methoxyphenam-
ine hydrochloride, an antiasthmatic drug (Scheme 1). Am-
phetamine and prenylamine lactic acid, for the treatment of
brain dysfunction in children and angina, respectively, are
both synthesized by using 1-phenylacetone as a starting
material.
Because of their synthetic value, a number of methods
have been developed for the preparation of arylacetones.4
One interesting synthetic route brought to our attention is
that using benzyl chloride derivatives as starting materials
to prepare benzylzinc(II) chloride derivatives that undergo
nucleophilic addition with acetic anhydride to give arylace-
tones (Scheme 2). However, two aspects of this synthetic
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

B
X. He et al.
Letter
Synlett
H2NO2S
O
O
O
HCl
COOH
HO
HO
N
H
NH2
tamsulosin hydrochloride
methyldopa
O
O
O
O
O
1-(4-methoxyphenyl)acetone
1-(3,4-dimethoxyphenyl)acetone
O
O
O
O
R
O
arylacetone
O
piperonyl methyl ketone
1-(2-methoxyphenyl)acetone
O
O
OH
HCl
HN
phenylacetone
O
N
H
methoxyphenamine hydrochloride
OH
prenylamine lactic acid
NH2
amphetamine
Scheme 1 1-Arylacetones as key intermediates for drugs
ing the carboxylic acid group of (E)-3-aryl-2-methylacrylic
acids into an amino group through a Curtius rearrangement
(Scheme 3).
As the Curtius rearrangement is one of our interests,
and because (E)-3-aryl-2-methylacrylic acids are widely
available,11,12 we developed a convenient and effective pro-
tocol for the synthesis of arylacetones by a one-pot two-
step reaction of (E)-3-aryl-2-methylacryloyl chlorides with
sodium azide, followed by hydrolysis in aqueous medium.13
In our previous work, we reported the preparation of
arylacetones from (E)-3-aryl-2-methylacrylic acids through
diazotization of the corresponding (E)-3-aryl-2-methylac-
ryloyl hydrazines, Curtius rearrangement, and hydrolysis.14
In this synthetic route, the formation of (E)-3-aryl-2-meth-
ylacryloyl hydrazines from (E)-3-aryl-2-methylacrylic acids
requires an additional esterification step before hydrazino-
lysis, making the method more complicated and less practi-
cal.
The Curtius rearrangement is an effective reaction for
the preparation of amino derivatives, and a number of
methods have been developed to synthesize acyl azides
from carboxylic acid derivatives.5 Acyl azides are initially
converted into isocyanates by rearrangement, and the iso-
cyanates subsequently react with various compounds to
form amine derivatives with one fewer carbon atom. Al-
though the Curtius rearrangement has been applied in a
number of organic transformations, such as the syntheses
of 2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide,6 tyra-
mine,7 sulfonylureas,8 oseltamivir (Tamiflu),9 and alkyl N-
(1-cyclohex-3-enyl)carbamates,10 to the best of our knowl-
edge, its application in the synthesis of arylacetones has not
been reported.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

C
X. He et al.
Letter
Synlett
OH
R
R
Zn
Ac2O
Cl
ZnCl
R
R
R
THF
O
H3O+
THF Mg
MeCN
MgCl
R
R
NMgCl
R
R
Scheme 2 Two routes to arylacetones by nucleophilic addition reactions
This was followed by the direct addition of 20% aqueous so-
dium azide (1.01 equiv) directly to the above system at
room temperature under vigorous stirring for another 30
minutes. The mixture was then refluxed for the specified
time (Scheme 4). To obtain a better yield, key factors in the
reaction were optimized by monitoring the yield of the
products (Table 1). Three reaction media (dichloromethane,
chloroform, and carbon tetrachloride) and two reaction
times (3 and 1.5 hours) were tested during the optimiza-
tion. Dichloromethane emerged as the worst solvent, giving
only 11% yield of 1-phenylacetone (Table 1, entry 1). Adding
tetrabutylammonium bromide (TBAB) as a surfactant dou-
bled the yield (entry 2). On changing the reaction medium
to chloroform or carbon tetrachloride containing a catalytic
amount of TBAB, yields of 62% and 93% were obtained after
1.5 hours (entries 3 and 4).
NH
R
R
O
COOH
NH2
R
R
Scheme 3 Proposed route for converting (E)-3-aryl-2-methylacrylic
acids into arylacetones
Acyl azides can also be obtained in satisfactory yields by
acylation of sodium azide with acyl chlorides.5d–g (E)-3-
Aryl-2-methylacryloyl chlorides are relatively stable in wa-
ter at low temperatures, so we envisaged that aqueous sodi-
um azide might be used as a source of azide to react with
(E)-3-aryl-2-methylacryloyl chlorides to generate (E)-3-
aryl-2-methylacryloyl azides that would undergo subse-
quent Curtius rearrangement and hydrolysis in one pot.
As a typical example, the synthesis of (E)-2-methyl-3-
phenylacryloyl chloride was initiated by adding thionyl
chloride (1.01 equiv) to a (E)-2-methyl-3-phenylacrylic acid
solution in various reaction media at 35 °C for 30 minutes.
COOH
1. SOCl2
O
2. 20 mol% NaN3, reflux
2a
1a
Scheme 4 Preparation of 1-phenylacetone
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

D
X. He et al.
Letter
Synlett
Table 1 Optimization of the Reaction Conditions
Table 2 Synthesis of 1-Arylacetones 2a–i
COOH
Entry
Reaction medium
Reflux time (h)
Yield (%)
1. SOCl2, CCl4
R
R
O
2. 20 mol% NaN3
10 mol% TBAB
reflux
1
2
3
4
5
CH2Cl2
3
11
25
62
93
90
1
2
CH2Cl2 + TBAB (10 mol%)
CHCl3 + TBAB (10 mol%)
CCl4 + TBAB (10 mol%)
DCE + TBAB (10 mol%)
3
1.5
1.5
1.5
Entry
Product
R
Timea (h)
Yield (%)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
H
1.5
1.5
1.5
1.5
1.5
2
93
86
82
87
89
85
88
85
83
3,4,5-(MeO)3
3,4-(MeO)2
4-MeO
2-MeO
3-O2N
4-O2N
3-Cl
The best yield (93%) of 1-phenylacetone (2a) was ob-
tained with carbon tetrachloride as the reaction medium
(entry 4); this might be due to the high boiling point of this
solvent, as the Curtius rearrangement requires a relatively
high temperature. The use of refluxing carbon tetrachloride
as a reaction medium is sufficient to provide the activation
energy necessary for the rearrangement of acyl azides,
leading to completion of the rearrangement reaction, there-
by increasing the reaction rate and yield. The reaction tem-
perature is therefore a key factor in determining the reac-
tion rate and the product yield. To confirm this finding, we
used DCE as a medium, and we found that with the same
reaction time, a similar yield (90%) of 1-phenylacetone (2a)
was obtained (entry 5).
2g
2h
2i
2
1.5
1.5
4-Cl
a Reflux time in step 2.
Supporting Information
With the optimized conditions in hand, we investigated
the synthesis of a group of 1-arylacetones from various (E)-
3-aryl-2-methylacrylic acids as starting materials (Table
2).15 The reactions proceeded smoothly in all cases, giving
the corresponding products 2a–i in yields of 82–93% (Table
2, entries 1–9). No distinct substituent effect of the (E)-3-
aryl-2-methylacrylic acid substrates was observed, and
substrates with electron-donating or electron-withdrawing
groups gave the corresponding products in good yields and
in similar reaction times (1.5–2 h). This, therefore, is a
unique route for the preparation of several of 1-arylace-
tones.
In conclusion, a convenient and efficient method was
developed for the preparation of arylacetones from (E)-3-
aryl-2-methylacrylic acids. The protocol permits both the
rearrangement of the (E)-3-aryl-2-methylacryloyl azides
and the subsequent hydrolysis to be carried out in one pot
under mild conditions. A series of 1-arylacetone derivatives
were synthesized successfully in yields of 82–93%. Further
optimization to broaden the scope and applications of this
method are currently underway, and will be reported in
due course.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588905.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
(1) (a) Yang, J. S.; Park, C.-H.; Lee, C.; Kim, H.; Oh, C.; Choi, Y.; Kang,
J. S.; Yun, J.; Jeong, J.-H.; Kim, M.-H.; Han, G. Eur. J. Med. Chem.
2014, 85, 399. (b) Sasaki, S.; Cho, N.; Nara, Y.; Harada, M.; Endo,
S.; Suzuki, N. J. Med. Chem. 2003, 46, 113. (c) Furuya, S.; Suzuki,
N.; Cho, N.; Nara, Y. WO 2000056739, 2000.
(2) Wyman, D. P.; Kaufman, P. R. J. Org. Chem. 1964, 29, 1956.
(3) (a) Hoorn, H. J.; Pis, J. WO 2003037851, 2003. (b) Wheeler, W. J.;
Schmiegel, K. K.; Hunden, D. C. J. Labelled Compd. Radiopharm.
1989, 27, 171. (c) Nichols, D. E.; Barfknecht, C. F.; Rusterholz, D.
B.; Benington, F.; Morin, R. D. J. Med. Chem. 1973, 16, 480.
(d) Hambuchen, M. D.; Carroll, F. I.; Rüedi-Bettschen, D.;
Hendrickson, H. P.; Hennings, L. J.; Blough, B. E.; Brieaddy, L. E.;
Pidaparthi, R. R.; Owens, S. M. J. Med. Chem. 2015, 58, 4665.
(e) Li, J. Y.; Hui, H. T.; Yi, Y.; Adams, J. P.; Snajdrova, R.; Li, Z. ACS
Catal. 2015, 5, 1119.
(4) (a) Zsolczai, D.; Németh, J.; Hell, Z. Tetrahedron Lett. 2015, 56,
6389. (b) Xu, Y.; Hu, X.; Shao, J.; Yang, G.; Wu, Y.; Zhang, Z. Green
Chem. 2015, 17, 532. (c) Li, S.; Huang, K.; Zhang, X. Chem.
Commun. 2014, 50, 8878. (d) Kuchař, M.; Brunová, B.; Rejholc,
V.; Jelínková, M.; Holubek, J.; Němeček, O. Collect. Czech. Chem.
Commun. 1984, 49, 122. (e) Catalano, J. G.; Gaitonde, V.; Beesu,
M.; Leivers, A. L.; Shotwell, B. Tetrahedron Lett. 2015, 56, 6077.
(f) Zimbron, J. M.; Seeger-Weibel, M.; Hirt, H.; Gallou, F. Synthe-
sis 2008, 1221.
(5) (a) Reddy, P. S.; Yadagiri, P.; Lumin, S.; Shin, D.-S.; Falck, J. R.
Synth. Commun. 1988, 18, 545. (b) Lee, J. G.; Kwak, K. H. Tetrahe-
dron Lett. 1992, 33, 3165. (c) Lago, J. M.; Arrieta, A.; Palomo, C.
Synth. Commun. 1983, 13, 289. (d) Gumaste, V. K.; Bhawal, B. M.;
Acknowledgment
This work was supported by the National Natural Science Foundation
of China (Grant No.81274128, 81573687) and the project of Liaoning
Distinguished Professor.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

E
X. He et al.
Letter
Synlett
Deshmukh, A. R. A. S. Tetrahedron Lett. 2002, 43, 1345.
(e) Akhlaghinia, B.; Rouhi-Saadabad, H. Can. J. Chem. 2013, 91,
181. (f) Rewcastle, G. W.; Denny, W. A. Synthesis 1985, 220.
(g) Luedtke, A. E.; Timberlake, J. W. J. Org. Chem. 1985, 50, 268.
(h) Rawal, V. H.; Zhong, H. M. Tetrahedron Lett. 1994, 35, 4947.
(6) Ivanova, E. M.; Borovika, D. A.; Vozny, I. V.; Trapencieris, P.;
Žalubovskis, R. Chem. Heterocycl. Compd. (Engl. Transl.) 2012, 48,
1114.
(7) Li, Y.; Yang, F.; Xu, X.; Pan, S.; Wang, L.; Xia, C. Chin. J. Chem.
2009, 27, 433.
(8) Luckhurst, C. A.; Millichip, I.; Parker, B.; Reuberson, J.; Furber, M.
Tetrahedron Lett. 2007, 48, 8878.
1-(3,4,5-Trimethoxyphenyl)acetone(2b)
Faintly yellow solid; yield: 5.78 g (86%), mp 88–91 °C. 1H NMR
(600 MHz, DMSO-d6): δ = 6.49 (s, 2 H), 3.74 (s, 6 H), 3.66 (s, 2 H),
3.63 (s, 3 H), 2.11 (s, 3 H). 13C NMR (151 MHz, DMSO-d6): δ =
206.4, 153.1, 136.6, 130.9, 107.2, 60.3, 56.1, 50.3, 29.7. GC-MS
(EI): m/z = 224.2 [M+].
1-(3,4-Dimethoxyphenyl)acetone (2c)
Yellow oil; yield: 4.78 g (82%). 1H NMR (600 MHz, DMSO-d6):
δ = 6.87 (d, J = 8.1 Hz, 1 H), 6.78 (d, J = 1.9 Hz, 1 H), 6.70 (dd, J =
8.1, 2.1 Hz, 1 H), 3.72 (s, 6 H), 3.64 (s, 2 H), 2.09 (s, 3 H). 13C NMR
(151 MHz, DMSO-d6): δ = 206.7, 149.0, 148.0, 127.7, 121.9,
113.7, 112.2, 55.8, 55.8, 49.7, 29.5. GC-MS (EI): m/z = 194.2 [M+].
1-(4-Methoxyphenyl)acetone (2d)
(9) Yamatsugu, K.; Kamijo, S.; Suto, Y.; Kanai, M.; Shibasaki, M. Tet-
rahedron Lett. 2007, 48, 1403.
(10) Gómez-Sánchez, E.; Marco-Contelles, J. Tetrahedron 2005, 61,
1207.
Yellow oil; yield: 4.29 g (87%). 1H NMR (600 MHz, DMSO-d6):
δ = 7.08–7.11 (m, 2 H), 6.84–6.89 (m, 2 H), 3.72 (s, 3 H), 3.66 (s,
2 H), 2.08 (s, 3 H). 13C NMR (151 MHz, DMSO-d6): δ = 206.7,
158.4, 130.9, 127.2, 114.1, 55.3, 49.2, 29.6. GC-MS (EI): m/z =
164.2 [M+].
(11) (a) Verma, R. K.; Singla, R.; Punniyakoti, V. T. Med. Chem. Res.
2004, 13, 660. (b) Yan, Q.; Kong, D.; Li, M.; Hou, G.; Zi, G. J. Am.
Chem. Soc. 2015, 137, 10177. (c) Muhammad, N.; Tahir, M. N.;
Ali, S.; Zia-ur-Rehman, Acta Crystallogr., Sect. E 2008, 64, o1717.
(d) Kandukuri, S. R.; Schiffner, J. A.; Oestreich, M. Angew. Chem.
Int. Ed. 2012, 51, 1265. (e) Miyanaga, W.; Shima, Y.; Noguchi,
M.; Oonuki, A.; Kawato, Y.; Iwata, H.; Harada, E.; Takashita, R.;
Ueno, H.; Nakagawa, T. US 20110082109, 2011. (f) Cueva, J. P.;
Gallardo-Godoy, A.; Juncosa, J. I. Jr.; Vidi, P. A.; Lill, M. A.; Watts,
V. J.; Nichols, D. E. J. Med. Chem. 2011, 54, 5508.
1-(2-Methoxyphenyl)acetone (2e)
Yellow oil; yield: 4.39 g (89%). 1H NMR (600 MHz, DMSO-d6):
δ = 7.19–7.26 (m, 1 H), 7.12 (d, J = 7.3 Hz, 1 H), 6.96 (d, J = 8.3
Hz, 1 H), 6.88 (t, J = 7.3 Hz, 1 H), 3.73 (s, 3 H), 3.64 (s, 2 H), 2.07
(s, 3 H). 13C NMR (151 MHz, DMSO-d6): δ = 206.2, 157.5, 131.5,
128.6, 124.2, 120.6, 111.0, 55.7, 45.0, 29.7. GC-MS (EI): m/z =
164.2 [M+].
1-(3-Nitrophenyl)acetone (2f)
(12) The various (E)-3-aryl-2-methylacrylic acids were obtained
from commercial sources.
(13) 1-Arylacetones 2a–i; General Procedure
Yellow solid; yield: 4.57 g (85%); mp 64–66 °C. 1H NMR (600
MHz, DMSO-d6): δ = 8.04–8.11 (m, 2 H), 7.54–7.65 (m, 2 H),
4.00 (s, 2 H), 2.19 (s, 3 H). 13C NMR (151 MHz, DMSO-d6): δ =
205.5, 148.0, 137.6, 137.1, 129.8, 124.8, 121.8, 48.7, 30.1. GC-MS
(EI): m/z = 179.2 [M+].
A well-stirred mixture of the appropriate (E)-3-aryl-2-methyl-
acrylic acid 1 (30 mmol) and SOCl2, (30.3 mmol) in CCl4 (50 mL)
was heated at 35 °C for 30 min. 20% aq NaN3 (30.3 mmol) and
TBAB (0.97 g, 10 mol%) were added at r.t., and the mixture was
stirred for another 30 min, then heated to the reflux tempera-
ture. When the reaction was complete (1.5–2 h; Table 2), the
aqueous layer was separated and extracted with CCl4 (3 × 20
mL). The organic layers were combined, dried (Na2SO4), and
concentrated under reduced pressure. The residue was purified
by flash chromatography (silica gel, EtOAc–PE). All products
were identified by 1H and 13C NMR and MS spectral analysis.
(14) Meng, F.; He, X.; Cao, C.; Liang, J.; Zhang, T. CN 201610328295.4,
2016.
1-(4-Nitrophenyl)acetone (2g)
Faintly yellow solid; yield: 4.73 g (88%); mp 203–206 °C. 1H
NMR (600 MHz, DMSO-d6): δ = 8.12–8.21 (m, 2 H), 7.37–7.51
(m, 2 H), 3.99 (s, 2 H), 2.19 (s, 3 H). 13C NMR (151 MHz, DMSO-
d6): δ = 205.2, 146.7, 143.5, 131.5, 123.5, 49.2, 30.2. GC-MS (EI):
m/z = 179.2 [M+].
1-(3-Chlorophenyl)acetone (2h)
Yellow oil; yield: 4.30 g (85%). 1H NMR (600 MHz, DMSO-d6):
δ = 7.32 (t, J = 7.7 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 1 H), 7.26 (s, 1 H),
7.13 (d, J = 7.3 Hz, 1 H), 3.80 (s, 2 H), 2.14 (s, 3 H). 13C NMR (151
MHz, DMSO-d6): δ = 205.7, 137.8, 133.2, 130.3, 129.9, 128.8,
126.8, 49.1, 30.0. GC-MS (EI): m/z = 168.6 [M+].
(15) 1-Phenylacetone (2a)
Colorless oil; yield: 3.75 g (93%). 1H NMR (600 MHz, DMSO-d6):
δ = 7.29–7.34 (m, 2 H), 7.22–7.26 (m, 1 H), 7.18–7.21 (m, 2 H),
3.75 (s, 2 H), 2.12 (s, 3 H). 13C NMR (151 MHz, DMSO-d6): δ =
206.2, 135.3, 130.0, 128.7, 126.9, 50.0, 29.7. GC-MS (EI): m/z =
134.2 [M+].
1-(4-Chlorophenyl)acetone (2i)
Yellow oil; yield: 4.20 g (83%). 1H NMR (600 MHz, DMSO-d6):
δ = 7.32–7.39 (m, 2 H), 7.14–7.24 (m, 2 H), 3.78 (s, 2 H), 2.13 (s,
3 H). 13C NMR (151 MHz, DMSO-d6): δ = 205.9, 134.3, 131.9,
131.7, 128.5, 49.0, 29.9. GC-MS (EI): m/z = 168.6 [M+].
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E